Abstract

Well-defined times for minimum and maximum growth rates of rat hepatoma 3924A were found when cyclophosphamide doses were increased from 50 to 250 mg/kg. Minimum growth rates occurred 8 to 10 days after treatment and maximum growth rates occurred 13 to 16 days after treatment in 5 groups of 10 animals each that received 50, 100, 150, 200, and 250 mg of cyclophosphamide per kg. Tumor growth delay increased from 6 to 18 days when the dose was increased from 50 to 250 mg/kg. The accelerated growth rate of treated tumors on Day 14 after cyclophosphamide (150 mg/kg) was more than twice that of controls on the same day, 0.349 ± 0.030 (S.E.) (day-1) and 0.156 ± 0.011 (day-1), respectively. In addition, the accelerated growth rate of treated tumors on Day 14 was greater than that of controls at initiation of treatment, 0.298 ± 0.026 (day-1) on Day 2. Increased DNA synthetic rate precedes increased tumor cell proliferation, which, in turn, increases tumor volume. Thus, biochemical studies demonstrating increased cellular proliferation confirm accelerated tumor growth following treatment.

Footnotes

↵1 Supported in part by a USPHS Research Emphasis Grant (CREG) CA20516 on Experimental Combined Modality (Radiotherapy-Chemotherapy) Studies (ECMRC) from the National Cancer Institute. This is Paper 18 in a series entitled, “Solid Tumor Models for the Assessment of Different Treatment Modalities.”

↵2 To whom requests for reprints should be addressed, at Box 392, University of Virginia Hospital, Charlottesville, Va. 22908.